Assessing aggressiveness of a given tumor sample can help physicians advise between aggressive treatment and active surveillance of the disease (e.g. in case of early stage breast cancer and prostate cancer). In such way only patients with aggressive disease get active treatment and patients with least aggressive disease can settle with active surveillance just to be sure that their disease does not progress (in such case chemotherapy, surgery, radiotherapy or other treatment, like hormone- or immunotherapy, is not applied leading to social and economic benefits).
Attempts have been made with methods for categorizing cancers based on the aggressiveness. For instance, US20160320316 discloses a method for determining, in vitro, aggressiveness grade of cancer cells originating from solid tissue suspected of being cancerous, wherein the categorizing is based on the electromagnetic signature of the cells. In US20020127619 a method of diagnosing stage or aggressiveness of breast and prostate cancer based on levels of fatty acid binding proteins is disclosed. Neither of the named methods have been taken into routine use by clinics. In standard clinical setting, immunohistochemistry has been widely used, but studies have shown significant discordance between results from different labs and even between different pathologists within a same lab. Therefore, predicting tumor aggressiveness has remained difficult and controversial.
In the present invention, time-dependent intracellular metabolite fluxes in the cytosol of cancer cells were studied. Differences in metabolite fluxes in samples of the same type (e.g. tumor samples) supported predictions for assessing metabolic activity (e.g. aggressiveness) of a given sample (e.g. expected need for aggressive therapy or active surveillance) or predicting response to treatment with drugs targeting pathways or enzymes contributing to fluxes that can be quantified using the method described below.
Oncological drugs often have low response rates due to intrinsic peculiarities between or within tumors that often cannot be predicted with standard methods. That is particularly true for drugs targeting mitochondrial metabolism in tumors. In case of mutant IDH (iso-citrate dehydrogenase) 1 and mutant IDH 2 the response rate in treated patients is up to 40%; in case of glutaminase inhibitors the response rate is lower. Treatment against mutant IDH is applied only among patients with the said mutation, but response rate in such setting is still as low as mentioned. For glutaminase inhibitors no confirmed biomarkers have been found to stratify patients and to increase response rate among treated patients. In such situation, the method described herein could be a valuable tool to stratify patients as the metabolic pathways that these drugs, among others, are affecting, can be directly measured and quantified in tumor samples prior to assigning them to treatment groups. Both surgical samples or biopsies can be used for the method described here.